Download More on the right ventricle in pulmonary hypertension Robert Naeije and Stefano Ghio

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EDITORIAL
PULMONARY VASCULAR DISEASES
More on the right ventricle in pulmonary
hypertension
Robert Naeije1 and Stefano Ghio2
Affiliations: 1Dept of Physiology, Erasme University Hospital, Brussels, Belgium. 2Dept of Cardiology,
Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Correspondence: Robert Naeije, Dept of Physiology, Erasme Campus CP 604, 808 Lennik road, B-1070
Brussels, Belgium. E-mail: [email protected]
@ERSpublications
Decreased RVEF and PVR is associated with a decreased survival rate in PAH patients under
targeted therapies http://ow.ly/EBK8U
In the present issue of the European Respiratory Journal, COURAND et al. [1] report on the prognostic
relevance of radionuclide angiography of the right ventricle (RV) in a cohort of 100 patients with
idiopathic, heritable or drug-related pulmonary arterial hypertension (PAH). Patients with a baseline RV
ejection fraction (RVEF) >25% had better survival than those with a RVEF <25%. Furthermore, patients
with a stable or increased RVEF at 3–6 months had a trend to better overall survival and a significantly
lower cardiovascular mortality. These results are in keeping with recently demonstrated prognostic
relevance of baseline and follow-up RVEF, but measured by magnetic resonance imaging (MRI) in PAH
patients [2]. A striking finding in both studies was the dissociation between RVEF and pulmonary vascular
resistance (PVR). Thus, a decreased PVR under targeted therapies could be associated with either
deterioration or improvement in RV function [1, 2]. The notion emerges that PAH is a disease of RV–
arterial uncoupling rather than only of pathological pulmonary vascular remodelling [3].
Right ventricular failure in pulmonary hypertension is the obvious consequence of prolonged exposure to
excessive afterloading [3]. So, how is it possible that patients with a treatment-induced decrease in PVR
might present with a worsening of RV function? The first possible answer is that the RV follows its own
course of adaptation or maladaptation in increased pulmonary artery pressure (PAP), with considerable
individual variation as a persistent, possibly genetic, biological mystery [4]. A second possible answer is in
the inevitable systemic effects of pulmonary vasodilators. This has already been discussed at a time when
PAH patients were tentatively treated with calcium channel blockers, hydralazine or minoxidil. All these
systemic vasodilators increased cardiac output with no significant change in pulmonary vascular pressures,
thus, decreased PVR. But associated increased systemic venous return would increase RV end-diastolic
volume (EDV), increase RV afterload because of an increased wall tension (estimated by EDV×PAP) and
decrease RVEF. SNIDERMAN and FITCHETT [5] called this the paradox of therapeutic success and clinical
failure. High normal cardiac output with unchanged PAP may also be observed with targeted therapies,
which thus have the potential of the unwelcome combination of decreased PVR and RVEF. It is not
known how often this happens and how clinically relevant this maybe. In any case, COURNAND et al. [1]
clearly demonstrate that one cannot be satisfied with PVR alone as a therapeutic goal in PAH.
The study by COURAND et al. [1] is reminiscent of the flurry of reports of radionuclide angiographic
measurements of RVEF in patients with chronic obstructive pulmonary disease (COPD), which were
published in the 1970s and 1980s [6–12]. About half of these patients had a RVEF <45–50%, which was
taken as the upper limit of normal [6–8]; a less stringent value than 30% considered by COURAND et al. [1].
One study reported failure of RVEF to rise during exercise, even in patients with a normal value at rest
[9]. This was globally interpreted as “cor pulmonale” or RV failure on lung diseases and/or hypoxia.
However, subsequent combined haemodynamic and radionuclide angiographic studies showed preserved
Received: Nov 11 2014 | Accepted: Nov 15 2014
Conflict of interest: None declared.
Copyright ©ERS 2015
Eur Respir J 2015; 45: 33–35 | DOI: 10.1183/09031936.00209414
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PULMONARY VASCULAR DISEASES | R. NAEIJE AND S. GHIO
systolic PAP to end-systolic volume (ESV) ratios [10], indicating preserved systolic function. RVEF was
found to be more tightly correlated to fluid retention (on hypercapnia) rather to the severity of pulmonary
hypertension [11]. RVEF predicted survival in COPD, but less significantly so than arterial blood gases or
altered lung mechanics [12]. As correlations between RVEF and PAP or PVR were variable, sometimes
tight [10] sometimes loose or even absent [6, 11], clinicians lost interest in radionuclide angiography of
the RV for the diagnosis of cor pulmonale or detection of pulmonary hypertension.
Is there a brighter future for radionuclide RVEF in PAH? Probably not. COURAND et al. [1] argue that
radionuclide angiography is affordable and widely available, and that radiation exposure is not a concern
except for repetitions in the youngest patients. However the procedure requires appointments at specialised
departments, with possible waiting lists, and age-independent unequivocal safety of repetitions of the
assessment of RV function is exactly what the follow-up of PAH requires. Furthermore, radionuclide
angiography is a planar measure of a three-dimensional (3D) change and suffers from somewhat arbitrary
automated contour definition. This explains variable and occasionally very low RVEF reported in normal
subjects.
COURAND et al. [1] selected a RVEF of 25% as critical for the separation between good and bad prognosis.
But this was a median value rather than a more methodologically correct sum of the highest specificity
and sensitivity derived from receiver-operating characteristic curves, which would probably have yielded an
even lower number. When RVEF was measured with MRI in similar PAH patients, a rigorously defined
cut-off of 35% was found [2].
So, what would currently be the best and most practical way to evaluate RV function in PAH? Right heart
catheterisation can measure stroke volume (SV) and right atrial pressure, but cannot measure RV volumes,
and is, therefore, an imperfect surrogate for gold standard RV function definition by pressure–volume
relationships [3, 13]. COURAND et al. [1] express disappointment about echocardiographic measurements
such as M-mode tricuspid annular plane systolic excursion or tissue Doppler imaging of the maximum
velocity of tricuspid annulus isovolumic contraction, both previously shown to be independent predictors
of outcome in severe PH [14, 15]. These turned out to be of little additional value to radionuclide RVEF
[1]. However, modern echocardiography of the RV includes several further measurements of structure and
function demonstrated to be of prognostic relevance [16] and nowadays preferably integrated in a
multi-parametric evaluation [17, 18]. Furthermore, developments in 3D-echocardiography open the
perspective of accurate RV volume measurements [19]. Thus, echocardiographic measurements of RVEF
are now possible, and have already been reported to be of prognostic relevance [20]. It has recently been
suggested that a SV/ESV rather than SV/EDV, i.e. ejection fraction, may be a less preload-dependent
estimate of RV function, and superior for the prognostication of patients with pulmonary hypertension
[21]. This requires confirmation and can be further explored by bedside 3D-echocardiography.
Further added value of both MRI and echocardiography is insight into regional function and dyssynchrony
(or inter-regional changes in strain and velocity of contraction) and asynchrony (or delaying of RV systole
into left ventricular diastole), also called “post-systolic shortening” [22–24]. Regional RV function is
efficiently explored by speckle tracking echocardiography, which evolves from 2D [25] to improved 3D
[20] assessments. Speckle tracking echocardiography still requires time-consuming off-line analyses, but
opens a fascinating perspective for further noninvasive and flexible research on RV function integrated
into the daily practice of echocardiography [26].
The understanding of RV function in severe pulmonary hypertension is making rapid progress.
Radionuclide angiography has delivered, but is now being replaced by MRI and 3D-echocardiography. In
this context, COURAND et al. [1] are to be commended for their enlightening contribution to the
understanding of PAH as a RV failure syndrome.
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